Histone Deacetylase Inhibitors Impair Glioblastoma Cell Motility and Proliferation

Despite being subjected to high-dose chemo and radiotherapy, glioblastoma (GBM) patients still encounter almost inevitable relapse, due to the capability of tumor cells to disseminate and invade normal brain tissues. Moreover, the presence of a cancer stem cell (CSC) subpopulation, already demonstra...

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Veröffentlicht in:Cancers 2022-04, Vol.14 (8), p.1897
Hauptverfasser: Rampazzo, Elena, Manfreda, Lorenzo, Bresolin, Silvia, Cani, Alice, Mariotto, Elena, Bortolozzi, Roberta, Della Puppa, Alessandro, Viola, Giampietro, Persano, Luca
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Sprache:eng
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Zusammenfassung:Despite being subjected to high-dose chemo and radiotherapy, glioblastoma (GBM) patients still encounter almost inevitable relapse, due to the capability of tumor cells to disseminate and invade normal brain tissues. Moreover, the presence of a cancer stem cell (CSC) subpopulation, already demonstrated to better resist and evade treatments, further frustrates potential therapeutic approaches. In this context, we previously demonstrated that GBM is characterized by a tightly-regulated balance between the β-catenin cofactors TCF1 and TCF4, with high levels of TCF4 responsible for sustaining CSC in these tumors; thus, supporting their aggressive features. Since histone deacetylase inhibitors (HDI) have been reported to strongly reduce TCF4 levels in colon cancer cells, we hypothesized that they could also exert a similar therapeutic action in GBM. Here, we treated primary GBM cultures with Trichostatin-A and Vorinostat, demonstrating their ability to strongly suppress the Wnt-dependent pathways; thus, promoting CSC differentiation and concomitantly impairing GBM cell viability and proliferation. More interestingly, analysis of their molecular effects suggested a prominent HDI action against GBM cell motility/migration, which we demonstrated to rely on the inhibition of the RhoA-GTPase and interferon intracellular cascades. Our results suggest HDI as potential therapeutic agents in GBM, through their action on multiple cancer hallmarks.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14081897